Mechanism of competition between chloride and stilbenedisulfonates for binding to human erythrocyte band 3 (AE1)

Stilbenedisulfonates (S) constitute an important class of competitive inhib itors of the anion exchange (AE) function found in plasma membranes of vari ous cell types. I present a brief summary of recent kinetic studies that pr ovide insight into the mechanism of stilbenedisulfonate-chloride competitio n in binding to human erythrocyte band 3 (AE1) (B), the chloride-bicarbonat e exchanger. Reversible stilbenedisulfonate binding follows a two-step mech anism (S + B <-> SB <-> SB*). Several lines of evidence are summarized that show that chloride, stilbenedisulfonates, and band 3 form a ternary comple x, with chloride lowering stilbenedisulfonate affinity allosterically, by a ccelerating the rate of stilbenedisulfonate release. Of particular signific ance was our evidence demonstrating that extracellular chloride could accel erate stilbenedisulfonate release from its binding site on the outer surfac e of band 3 in resealed ghosts (i.e., acceleration in the release of a boun d competitive inhibitor by a cis substrate). I suggest that the latter resu lt may be consistent with our earlier proposal that band 3 follows a two-si te ordered sequential mechanism, where two allosterically linked chloride b inding transport sites move back and forth across the membrane together.